How does the brain process sensory information from internal organs?

Historically, however, very little research has been devoted to understanding these basic bodily sensations -- also known as internal sensations -- that arise when the brain receives and interprets input from internal organs

Now, a team led by researchers at Harvard Medical School has made new progress in understanding the basic biology of internal organ perception, which involves a complex cascade of communication between cells in the body

In a study in mice, published Aug.

They found that feedback from different organs activated discrete clusters of neurons, regardless of whether the information was mechanical or chemical in nature—these groups of neurons representing different organs were topographically organized in the brainstem

"Our study sheds light on the fundamentals of how different internal organs behave in the brainstem," said Chen Ran, the study's first author and a cell biology researcher at Harvard Medical School

This research is just the first step in elucidating how internal organs communicate with the brain

"I think understanding how sensory input is encoded by the brain is one of the biggest mysteries of how the brain works," said Stephen Liberles, a professor of cell biology at the Blavatnik Institute at Harvard Medical School and a Howard Hughes Medical Institute investigator.

Insufficient research, insufficient understanding

For nearly a century, scientists have been studying how the brain processes external information to form the basic senses of sight, smell, hearing, taste and touch we use to navigate the world

For example, in the mid-20th century, research into touch led scientists to develop the cortex homunculus of the somatosensory system—an illustration of cartoonized body parts overlaid on the surface of the brain, with each part positioned in relation to the way it is placed The locations of the treatments are aligned and scaled according to the sensitivity

However, until now, the process by which the brain senses and organizes feedback from internal organs to regulate basic physiological functions such as hunger, satiety, thirst, nausea, pain, breathing, heart rate and blood pressure has remained a mystery

"How the brain receives inputs from within the body and how it processes those inputs is far from well-studied and poorly understood," Liberles said

Professor Ran added that this may be because internal perception is more complex than external perception

In contrast, internal organs transmit information through mechanical forces, hormones, nutrients, toxins, temperature, etc.

group of neurons

In their new study, Liberles, Ran and colleagues focused on an area of ​​the brainstem known as the nucleus tractus solitarius (NTS)

It is reported that NTS receives sensory information from internal organs through the vagus nerve

The researchers used a powerful technique called two-photon calcium imaging to measure calcium levels in individual neurons in the brain as a proxy for neuronal activity

The team applied the technique to mice exposed to different types of internal organ stimulation and used microscopy to simultaneously record the responses of thousands of neurons in the NTS over time
.
The resulting video showed neurons glowing throughout the NTS, like twinkling stars in the night sky
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Traditional imaging techniques, which involve inserting an electrode to record a small group of neurons at a single time point, "are like seeing only a few pixels of an image at a time," Ran said
.
"Our technology is like seeing all the pixels at once, displaying the entire image in high resolution
.
"

The team found that stimulating different internal organs—for example, the stomach and larynx—generally activated different clusters of neurons in the NTS
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In contrast, the researchers found that, in several cases, mechanical and chemical stimulation of the same organ often triggered the same physiological response (such as coughing or satiety), activating overlapping neurons in the brainstem
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These findings suggest that specific neuronal populations may be specialized to represent specific organs
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In addition, the researchers found that NTS responses were organized into a spatial map, which they dubbed the "visceral homunculus," to echo a similar cortical homunculus that developed decades ago
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Finally, the scientists determined that signal transmission from internal organs to the brainstem requires neuronal inhibition
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When they used drugs to block inhibition, neurons in the brainstem began to respond to multiple organs, losing their preferential selectivity
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Professor Ran said the work lays the groundwork for a "systematic study of the encoding of senses within the entire brain"
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Lay the foundation for the future

The findings raise many new questions, some of which the Royal Naval Research Group wants to address
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Ran is interested in how the brainstem transmits internal sensory information to higher-order brain regions that produce feelings such as hunger, pain or thirst
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Liberles wants to explore how the internal sensing system works at the molecular level
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In particular, he wanted to identify the primary sensory receptors that detect mechanical and chemical stimuli within the organ
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Another area for future research is how the system is established during embryonic development
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The new findings show that looking at neuron types alone isn't enough; researchers must also consider where neurons are located in the brain, Liberles said
.

"We need to study the interactions between neuron types and their locations to understand how circuits are wired and what different cell types do in different circuit contexts," he said
.

Liberles is also interested in how well the findings generalize to other animals, including humans
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He noted that while many sensory pathways are conserved across species, there are also important evolutionary differences
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For example, some animals do not exhibit basic behaviors such as coughing or vomiting
.

If confirmed in humans, the findings could ultimately help develop better treatments for diseases caused by malfunctioning internal sensory systems
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Professor Ran said: "Usually these diseases occur because the brain receives abnormal feedback from internal organs
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If we get a good understanding of how these signals are encoded differently in the brain, we may one day be able to figure out how to hijack them the system, and restore normal function
.
"

Chen Ran, Jack C.
Boettcher, Judith A.
Kaye, Catherine E.
Gallori, Stephen D.
Liberles.
A brainstem map for visceral sensations.
Nature, 2022